Association Study On Vitiligo Immune Susceptible Gene In Chinese Han Population With Other Autoimmune Diseases

Background Vitiligo is the most common depigmentary disorder resulting from the loss of the melanocytes in the skin. At present, the onset of vitiligo is still not clear, mainly includes the theory of melanocyte self-destruction, biological theory, theory of nerve, immunology and genetic theory itself, etc., and autoimmune theory was identified by more and more studies. In recent years, GWAS were used to study the susceptibility genes of complex diseases. In Europe and in China, there are two main team used the research methods of GWAS, they found some susceptibility genes associated with vitiligo, and verified in different populations. Mainly includes SNPS on SMOC2, PTPN22, RERE, C1QTNF6, GZMB, these immune susceptibility loci were associated with vitiligo. Some genes are correlated to immune regulation and highly with other autoimmune diseases such as autoimmune thyroid disease, rheumatoid arthritis. So far, there were about seventy SNPS associated with vitiligo. However, some of them have not replicated in the Chinese Han population of vitiligo concomitant occurrence of other autoimmune diseases.Objective To examine whether the seventeen loci on ATP8B1, CLNK, LPP, GZMB, IKZF4, RPGRIP1 L, CASP7, CD80, IL2 RA were associated with susceptibility to vitiligo concomitant occurrence of other autoimmune diseases in the Chinese Han population.Methods Ten SNPs—rs10503019 at 18q21.31, rs11940117 at 4p16.1, rs1464510 at 3q28, rs2273844 at 14q12, rs2456973 at 12q13.2, rs3213758 at 16q12.2, rs4353229 at10q25.3, rs59374417 at 3q13.33, rs706779 and rs7090530 at 10p15.1 were genotyped in 552 patients with autoimmune diseases and 1,656 controls using the Sequenom Mass Array system. Data were analyzed with PLINK 1.07 software.Results 1. In association analyses, the C allele of rs2456973 at 12q13.2 was observed to be significantly associated with vitiligo-associated autoimmune diseases(P=0.003, OR=1.27, 95% CI= 1.09-1.48). Allele C of the SNP rs11940117 at 4p16.1 might be associated with vitiligo-associated autoimmune diseases(P=0.01, OR=0.83, 95% CI= 0.72-0.96).2. In subphenotype analyses, the rs2456973 C allele was significantly associated with early onset(P=0.01, OR=0.67, 95% CI=0.49-0.92). Rs11940117 especially was associated with vitiligo accompanying rheumatoid arthritis(P=0.04, OR=0.63, 95% CI=0.40-0.98).Conclusion We confirmed that 12q13.2 was an important candidate locus for vitiligo-associated autoimmune diseases and affected disease phenotypes with early-onset. Locus 4p16.1 might be the candidate one to vitiligo-associated autoimmune diseases and affected disease phenotypes with rheumatoid arthritis.